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The William Harvey Research Institute - Barts and The London

Professor Christoph Thiemermann

Christoph

Centre Lead for Translational Medicine and Therapeutics

Centre: Translational Medicine and Therapeutics

Email: c.thiemermann@qmul.ac.uk
Telephone: +44(0) 20 7882 2121

Profile

Chris Thiemermann is Professor of Pharmacology and Centre Lead for Translational Medicine & Therapeutics at the William Harvey Research Institute (WHRI). He graduated with honours in Medicine (1986), obtained his MD in Medicine (1987, summa cum laude) from the University in Cologne in Germany (awarded University Prize 1987 for ’Best Doctorate Degree of all Faculties of the University of Cologne’) and received consecutive Fellowships from the Deutsche Forschungsgemeinschaft (DFG) and the Thyssen Foundation (Germany). He joined the WHRI in July 1987, where he obtained a PhD in Pharmacology under the supervision of The Nobel Laureate Sir John Vane in 1991. Thiemermann is an internationally recognised expert in pathophysiology and experimental therapy of shock and ischaemia-reperfusion injury (kidney and heart) with expertise in target discovery and evaluation of the efficacy of drugs in small animal models. His research was recognised the Sandoz Prize (British Pharmacological Society 1994), YIA of the Surgical Infection Society Europe (1999) and the Menarini-Award for CV Research (2001). Recent translational successes include a phase II RCTs evaluating the effects of pentoxiphylline in patients with chronic kidney disease (on dialysis) and the repurposing of the antimalarial drug artesunate for patients with severe haemorrhage and organ failure.

Over the years, Thiemermann’s research has been generously supported by the British Heart Foundation (Senior Fellow from 1996 to 2001), The Wellcome Trust, British Pharmacological Society, the European Union, the Medical Research Council, Kidney Research UK and William Harvey Research Foundation, Barts and the London Charity (BLC), BBSRC and the National Institute for Health Research (NIHR). He is currently a PI responsible for Vascular Inflammation and Regenerative Medicine in the NIHR-funded Barts BRU, Deputy Director of the BLC-funded Centre for Diabetic Kidney Disease and a co-PI in the BLC-funded Centre for Trauma Sciences at the Royal London Hospital. He has published more than 400 scientific articles in peer-reviewed scientific journals, which have been cited more than 28,000-times (h-index>88). According to Google Scholar, he is one of the thirty most cited pharmacologists in the world. He is a Fellow of the Academy of Medical Sciences of the United Kingdom, a Fellow of the British Pharmacological Society, a Foreign Member of the Academy of Sciences of Portugal (Lisboa), a Chair of the Post-Doctoral Fellowships Committee of the NIHR, Past-President of the European Shock Society (presidency 2008-2011), Member of the Executive Council of the World Federation of Shock Societies, Senior Associate Editor (Europe) of the Journal Shock (since 2003) and Chief Executive Officer (since 2003) of William Harvey Research Limited, a company that aids many pharmaceutical companies in the testing of the efficacy of NCEs in clinically relevant animal models of disease.

Research

Group members

Mr Gareth Purvis, Dr Lukas Martin, Dr Jianmin Chen, Miss Sura Al-Zoubi, Miss Catherine Murphy, Dr Noriaki Yamada, Mr William Hull.

Summary

We have a long-standing research interest in the pathophysiology and experimental therapy (preclinical and clinical) of (i) ischaemia-reperfusion of the heart (acute myocardial infarction,non-STEMI) and kidney (acute kidney injury, chronic kidney disease, renal fibrosis), and (ii) shock of variousaetiologies (septic shock, trauma-haemorrhage) and the associated systemic inflammation and multiple organ dysfunction syndrome. Over the years, we have identified several, new drug-able targets including inducible nitric oxide synthase (iNOS), poly (ADP-ribose) polymerase (PARP),peroxisome-proliferator activated receptors (PPARs), to name but a few. We have also developed and evaluated the efficacy of numerous, novel interventions for shock and ischaemia-reperfusion injury (including iNOS-inhibitors, PARP-inhibitors, radical scavengers, PPAR-ligands, non-haematopoietic analogues of erythropoietin and stem cells). More recently as part of the NIHR-funded Barts-BRU, the Centre for Trauma Sciences and the Centre for Diabetic Kidney Disease, we have focused on the development of highly translatable repositioning strategies.

Recent translational successes include phase II placebo-controlled randomised clinical trials (RCT) aimed at (a) evaluating the effects of pentoxiphylline in patients with chronic kidney disease on dialysis (together with Prof Magdi Yaqoob, Centre for Diabetic Kidney Disease) and (b) the repurposing of the antimalarial drug artesunate for patients with severe haemorrhage and organ failure (together with Prof Karim Brohi, Centre for trauma Sciences). The figure documents that the anti-malarial drug artesunate reduces the organ injury and dysfunction caused by severe blood loss and resuscitation in a preclinical model:

Figure 1. Artesunate attenuates the organ injury and dysfunction induced by HS. A, creatinine clearance; B, serum creatinine; C, serum AST; D, serum alanine ALT. Data are presented as box and whiskers, showing medians, interquartile range, and full range (n ¼ 10 animals per group). When necessary (as lipase data), the values had been transformed into logarithms to achieve normality and homogeneity of variances. Statistical analysis was performed using 1-way ANOVA followed by Bonferroni post hoc test. P < 0.05 vs sham þ vehicle and # P < 0.05 vs HS þ vehicle. ANOVA indicates analysis of variance; CK, creatine kinase.

Key Publications

  • Martin L, Horst K, Chiazza F, Oggero S, Collino M, Brandenburg K, Hildebrand F, Marx G, Thiemermann C, Schuerholz T. The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis. Sci Rep. 2016 Nov 17;6:37277. (Impact Factor: 5.2)
  • Coldewey SM, Benetti E, Collino M, Pfeilschifter J, Sponholz C, Bauer M, Huwiler A, Thiemermann C. Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. Sci Rep. 2016 Jun 9;6:27594. (Impact Factor: 5.2)
  • Chen J, Kieswich JE, Chiazza F, Moyes AJ, Gobbetti T, Purvis GS, Salvatori DC, Patel NS, Perretti M, Hobbs AJ, Collino M, Yaqoob MM, Thiemermann C. IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKD. J Am Soc Nephrol. 2016 May 6. (Impact Factor: 9.3)
  • Sordi R, Nandra KK, Chiazza F, Johnson FL, Cabrera CP, Torrance HD, Yamada N, Patel NS, Barnes MR, Brohi K, Collino M, Thiemermann C. Artesunate Protects Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation. Ann Surg. 2016 Feb 1. (Impact Factor: 8.3)
  • Coldewey SM, Khan AI, Kapoor A, Collino M, Rogazzo M, Brines M, Cerami A, Hall P, Sheaff M, Kieswich JE, Yaqoob MM, Patel NS, Thiemermann C. Erythropoietin attenuates acute kidney dysfunction in murine experimental sepsis by activation of the β-common receptor. Kidney Int. (2013) 84:482-90. (Impact Factor: 7.9)
  • Coldewey SM, Rogazzo M, Collino M, Patel NS, Thiemermann C. Inhibition of IκB kinase reduces the multiple organ dysfunction caused by sepsis in the mouse. Dis Model Mech. (2013) 6:1031-42. (Impact Factor: 5.0)
  • Nandra KK, Collino M, Rogazzo M, Fantozzi R, Patel NS, Thiemermann C. Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock. Dis Model Mech. (2013) 6:701-9 (Impact Factor: 5.0)
  • Byrne CJ, McCafferty K, Kieswich J, Harwood S, Andrikopoulos P, Raftery M, Thiemermann C, Yaqoob MM. Ischemic conditioning protects the uremic heart in a rodent model of myocardial infarction. Circulation. (2012) 125:1256-65. (Impact Factor: 14.1)
  • Kapoor A, Shintani Y, Collino M, Osuchowski MF, Busch D, Patel NS, Sepodes B, Castiglia S, Fantozzi R, Bishop-Bailey D, Mota-Filipe H, Yaqoob MM, Suzuki K, Bahrami S, Désvergne B, Mitchell JA, Thiemermann C. Protective Role of Peroxisome Proliferator-Activated Receptor-{beta}/{delta} in Septic Shock. Am J Respir Crit Care Med. (2010) 182:1506-15. (Impact Factor: 11.0)
  • Kumar S, Allen DA, Kieswich JE, Patel NS, Harwood S, Mazzon E, Cuzzocrea S, Raftery J, Thiemermann C, Yaqoob MM. Dexamethasone ameliorates renal ischemia-reperfusion injury. J Am Soc Nephrol. (2009) 20:2412-25. (Impact Factor: 9.3)
  • Collino M, Aragno M, Castiglia S, Tomasinelli C, Thiemermann C, Boccuzzi G, Fantozzi . Insulin reduces cerebral ischemia/reperfusion injury in the hippocampus of diabetic rats: a role for glycogen synthase kinase-3beta. Diabetes (2009) 58:235-42. (Impact Factor: 7.9)

Citation Report: 295 (from Web of Science Core Collection)

Sum of the Times Cited:18041 

Average Citations per Item:61.16

h-index:70 - i10-index: 351

Sponsors

William Harvey Research Foundation National Institute for Health Research  Biotechnology and Biological Scienes Research Council

Wellcome Trust      Queen Mary University of London  British Heart Foundation   Medical Research CouncilDepartment of Health

Collaborators

Internal: Professor Magdi Yaqoob (WHRI); Professor Karim Brohi (Blizzard Institute and Royal London Hospital); Professor Amrita Ahluwalia (WHRI); Professor Adrian Hobbs (WHRI); Professor Mauro Perretti (WHRI); Professor Sussan Nourshargh (WHRI); NIHR-funded Barts BRU; Professor Steffen Petersen (WHRI), Professor Ken Suzuki (WHRI)

External: Professor Michael Bauer (University of Jena, Germany); Professor Anthony Cerami (University of Leiden, The Netherlands); Prof Massimo Collino (University of Turin, Italy); Professor Andrea Huwiler (University of Bern, Switzerland); Professor Peter Radermacher (University of Ulm, Germany); Professor Fred Wong (National University of Singapore), Prof Gernot Marx (University of Aachen), Dr Sina Coldewey (University of Jena, Germany)